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•Human fibroblasts treated with barley β-glucan undergo a short proliferation arrest.•Knocking-down RB1 in fibroblasts abolishes the β-glucan-induced proliferation arrest.•Barley ...β-glucan improves detachment and migration of human fibroblasts.•Topical addition of barley β-glucan enhances wound healing of the mouse skin.
β-Glucans are considered candidates for the medication in different human pathologies. In this work, we have purified β-glucan from a selected barley line and tested their effects in primary human dermal fibroblasts. Unexpectedly, we have observed that this compound promoted a short-transitory proliferation arrest at 24 h after its addition on the medium. We have determined that this transitory arrest was dependent on the cell-cycle regulator protein Retinoblastoma. Moreover, dermal fibroblasts increase their migration capacities at 24 h after barley β-glucan addition. Also, we have described that barley β-glucan strongly reduced the ability of fibroblasts to attach and to spread on cell plates. Our data indicates that barley β-glucan signal induces an early response in HDF cells favoring migration versus proliferation. This feature is consistent with our observation that the topical addition of our barley β-glucan in vivo accelerates the wound closure in mouse skin.
Objective
To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type ...of components of ERAS play a key role on the decrease of surgical morbidity.
Materials and methods
We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate.
Results
Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (
p
< 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%,
p
= 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively,
p
= 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted RR = 0.815; 95% confidence interval (CI) 0.667–0.996;
p
= 0.045. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications.
Conclusions
Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS
Five barley chloroplast DNA microsatellites (cpSSRs) were used to study genetic relationships among a set of 186 barley accessions-34 Hordeum vulgare ssp. spontaneum (HS accessions) from Morocco, ...Ethiopia, Cyprus, Crete, Libya, Iraq, Iran, Turkey, Afghanistan and Israel, 122 H. vulgare ssp. vulgare landraces (HV landraces) from Spain, Bolivia (old Spanish introductions), Morocco, Libya and Ethiopia and 20 modern European spring barleys (HV cultivars). All loci were polymorphic in the material studied, with the number of alleles per locus ranging from two to three. Fifteen multi-locus haplotypes were observed, 11 in HS accessions and seven in HV landraces and cultivars. Of the seven haplotypes found in the HV lines, three were shared with the HS accessions, and four were unique. Cluster analysis revealed two main groups, one consisting of HS accessions from Ethiopia and the HV landraces from Spain, Bolivia (old Spanish), Morocco and Ethiopia, whereas the other larger group contained all of the other accessions studied. Based on these grouping and the existence of haplotypes found in the HV landraces and cultivars but not in the HS wild barley, a polyphyletic origin is proposed for barley, with further centres of origin in Ethiopia and the Western Mediterranean.
OBJECTIVESurvival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical ...recurrence (BR) or biochemical persistence (BP). MATERIALS AND METHODSRetrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml. A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. RESULTSMean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients. Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15years were 99.1%, 98.1% and 96.6%. Only time to BR <24months (HR=2.55, P=.01) was identified as an independent risk factor for RFS after SRT. CONCLUSIONSIn these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24months responded better to rescue treatment.
INTRODUCTIONThere are very few Spanish studies that compare oncological outcomes following radical prostatectomy (RP) based on surgical approach, and their methodology is not appropriate. OBJECTIVETo ...compare oncological outcomes in terms of surgical margins (SM) and biochemical recurrence (BR) between open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODSComparison of two cohorts (307 with ORP and 194 with LRP) between 2007-2015. Surgical margin status was defined as positive or negative, and BR as a PSA rise of >0.4 ng/ml after surgery. To compare the qualitative variables, we employed the Chi-squared test, and ANOVA was used for quantitative variables. We performed a multivariate analysis using logistic regression to evaluate the predictive factors of SM, and a multivariate analysis using Cox regression to evaluate the predictive factors of BR. RESULTSGleason 7 (3+4) was determined in the surgical specimens of 43.5% of patients, and 31.7% had positive SM. The most frequent pathological stage was pT2c, on the 61.9% of the cases. No significant differences were found between both groups, except for extracapsular extension (p=0.001), more frequent in LRP. The median follow-up was 49 months. BR was seen in the 23% of patients, without significant differences between groups. In the multivariable analysis, only the D'Amico risk group behaved as an independent predictive factor of positive SM, and Gleason score and positive SM acted as independent predictive factors of BR. CONCLUSIONThe surgical approach did not influence SM status or BR.
INTRODUCTIONMinimally invasive surgery regarding cystectomy has not had the same development as other urological surgeries. This could be due to the lack of published studies defining the advantages ...of this approach versus open surgery. OBJECTIVESThe main objective of this study is to establish the role of minimally invasive surgery, laparoscopic radical cystectomy, versus open surgery by analyzing their perioperative complications. MATERIAL AND METHODRetrospective cohort analysis of perioperative complications of 2homogeneous series of cystectomies: laparoscopic (n = 196) versus open (n = 197). Identification of independent predictors of perioperative complications by multivariate analysis. RESULTSIn the comparative analysis between laparoscopic cystectomies and open cystectomies we observed a lower rate of perioperative blood transfusion (P < 0.0001), a lower rate of global postoperative complications (P < 0.0001) and a lower rate of serious complications (Clavien > 3; P < 0.001) in the LRC group. There was also a lower mortality rate in the laparoscopic series compared to open ones (P < 0.0001). Surgical approach and surgical time (P < 0.001) were identified as independent predictors of complications. CONCLUSIONSWe have identified the laparoscopic approach as a complication shield for radical cystectomy. The open approach almost triples the risk of complications.
Mythimna unipuncta is a species with low susceptibility to the Bacillus thuringiensis (Bt) toxin, and this insect occasionally causes devastating damage to maize. In the study region, M. ...unipuncta‐developed larvae were observed moving from a non‐Bt crop to a nearby Bt crop. Although the first response of many caterpillars to xenobiotics, such as the Bt toxin, is to reduce food intake and prolong development, few studies have focused on the causes and consequences of this response in terms of resistance evolution. To clarify the causes of this response, this work compared changes in the feeding behaviour, cytochrome P450 expression and juvenile hormone titre during the last larval instar of M. unipuncta after Bt ingestion. Four P450 enzymes related to the xenobiotic metabolism of the CYP9 and CYP6 families were identified. Developed larvae fed the Bt diet reduced their food intake and CYP9 expression, experienced prolonged development and presented an altered juvenile hormone balance. The CYP9s were not increased in the larvae that consumed Bt, as previously expected, although their highest expression was observed when larval feeding increased. The high recovery capacity of the larvae contributed to their development when they were fed a non‐Bt diet. The efficiency of responses that act jointly as a defence mechanism against Bt might favour the development of field resistance to the toxin. Therefore, these responses should be further investigated for resistance management programmes.
How do caterpillars cope with xenobiotics? The case of Mythimna unipuncta, a species with low susceptibility to Bt
INTRODUCTIONRecurrence trends after renal cell cancer nephrectomy are not clearly defined. OBJECTIVETo evaluate recurrence trends according to recurrence risk groups (RRG). MATERIAL AND ...METHODRetrospective analysis of 696 patients with renal cell cancer treated with nephrectomy between 1990-2010. Three RRG were defined according to the presence of anatomopathological variables (pTpN stage, nuclear grade, tumor necrosis TN, sarcomatoid differentiation SD, positive resection margin RM): -Low RG (LRG): pT1pNx-0 G1-4, pT2pNx-0 G1-2; no TN, SD and/or RM (+). -Intermediate RG (IRG): pT2pNx-0 G3-4; pT3-4pNx-0 G1-2; LRG with TN. -High RG (HRG): pT3-4pNx-0 G3-4; pT1-4pN+; IRG with TN and/or SD; LRG with SD and/or RM (+). The Kaplan-Meier method has been used to evaluate recurrence-free survival as a function of RRG. The log-rank test was used to evaluate differences between survival curves. RESULTSThe median follow-up was 105 (IQR 63-148) months. Of the total series, 177 (25.4%) patients presented recurrence: distant 15.9%, local 4.9% and 4.6% distant and local. The recurrence rate varied according to the RRG with values of 72.9% for HRG, 16.9% for IRG and 10.2% for LRG (p=.0001). Most cases in LRG presented single organ recurrence (72.2%) (p=.006). The LRG experienced recurrence as single metastasis in 50% of cases, compared to 30% and 18.6% in IRG and HRG, respectively (p=.009). The most common sites of recurrence were lung and abdomen. Lung recurrence predominated in the HRG (72.9%) (p=.0001) and abdominal, in the LRG (83.3%) with a tendency to significance (p=.15). CONCLUSIONSRecurrence rates (especially bone and lung) increase with higher RG. Single organ recurrences and single metastases are more frequent in LRG.
INTRODUCTIONThere is no consensus on the follow-up protocol after nephrectomy for renal cell carcinoma (RCC), and the identification of recurrence risk groups (RRG) is required. OBJECTIVEEstablish ...recurrence risk groups (RRG). MATERIAL AND METHODA retrospective analysis of 696 patients with renal cancer submitted to surgery between 1990-2010; 568 (81.6%) patients treated with radical nephrectomy and 128 (18.4%) treated with partial nephrectomy. Pathological variables were classified as: 1st-level variables (1LPV): pTpN stage and Fuhrman grade (FG); and 2nd level pathological variables (2LPV): sarcomatoid differentiation (SD), tumor necrosis (TN), microvascular invasion (MVI) and positive surgical margins (PSM). Univariate and multivariate analysis have been performed using Cox regression to determine 1LPV related to recurrence. Based on 1LPV, we classified patients into three RRG: Low (LRG)<25%; Intermediate (IRG) 26-50% and High (HRG)>50%. We performed univariate and multivariate analysis with the 2LPVs for each RRG. With these data, patients were reclassified as RRG+. ROC curves were used for comparison of RRG and RRG+. RESULTSThe median follow-up was 105 months (range 63 to 148). There were 177 (25.4%) patients with recurrence: 111 (15.9%) distant, 34 (4.9%) local and 32 (4.6%) distant and local. In the multivariable analysis, Fuhrman grade (HR=2,75; P=.0001) and pTpN stage (HR=2,19; P=.0001) behaved as independent predictive variables of recurrence. Patients were grouped as RRG (AUC=0,76; p=0,0001): - LRG (pT1pNx-0 G1-4; pT2pNx-0 G1-2): 456 (65,5%) patients. - IRG (pT2pNx-0 G3-4; pT3-4pNx-0 G1-2): 110 (15,8%) patients. - HRG (pT3-4pNx-0 G3-4; pT1-4pN+): 130 (18,6%) patients. After multivariate analysis with 2LPV, RRG were reclassified (RRG+) (AUC=.84, P=.0001): -LRG+(LRG without TN, SD and/or PSM(+)). -IRG+(IRG; LRG with TN) -HRG+(HRG; LRG with SD and/or PSM(+); IRG with TN and/or SD) CONCLUSIONS: The inclusion of 2LPV to the classification according to VP1N improves the discriminating capacity of RRG classification.
OBJECTIVEBased on preoperative clinical and postoperative pathological variables, we aim to build a prediction model of cancer specific mortality (CSM) at 1, 3, and 5 years for patients with bladder ...transitional cell carcinoma treated with RC. MATERIAL AND METHODSRetrospective analysis of 517 patients with diagnosis of cell carcinoma treated by RC (1986-2009). Demographic, clinical, surgical and pathological variables were collected, as well as complications and evolution after RC. Comparative analysis included Chi square test and ANOVA technique. Survival analysis was performed using Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using logistic regression to identify the independent predictors of CSM. The individual probability of CSM was calculated at 1, 3 and 5 years according to the general equation (logistic function). Calibration was obtained by the Hosmer-Lemeshow method and discrimination with the elaboration of a ROC curve (area under the curve). RESULTSBC was the cause of death in 225 patients (45%). One, three and five-year CSM were 17%, 39.2% and 46.3%, respectively. The pT and pN stages were identified as independent prognostic variables of CSM at 1, 3 and 5 years. Three prediction models were built. The predictive capacity was 70.8% (CI 95% 65-77%, p=.000) for the 1st year, 73.9% (CI95% 69.2-78.6%, p=.000) for the third and 73.2% (CI% 68.5-77.9%, p=.000) for the 5th. CONCLUSIONSThe prediction model allows the estimation of CSM risk at 1, 3 and 5 years, with a reliability of 70.8, 73.9 and 73.2%, respectively.